title: Mutation hot spots in 5q31-linked corneal dystrophies.
abstract: Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant diseases of the human cornea: granular (Groenouw type I), Reis-Bücklers, lattice type I, and Avellino corneal dystrophies. All four diseases are characterized by both progressive accumulation of corneal deposits and eventual loss of vision. We have identified a specific recurrent missense mutation for each type of dystrophy, in 10 independently ascertained families. Genotype analysis with microsatellite markers surrounding the BIGH3 locus was performed in these 10 families and in 5 families reported previously. The affected haplotype could be determined in 10 of the 15 families and was different in each family. These data indicate that R555W, R124C, and R124H mutations occurred independently in several ethnic groups and that these mutations do not reflect a putative founder effect. Furthermore, this study confirms the specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5q.
authors.affiliation: Unit of Molecular Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Korvatska
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
authors.forename: A
authors.initials: A
authors.lastname: Djemaï
authors.forename: M X
authors.initials: MX
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Frueh
authors.forename: A G
authors.initials: AG
authors.lastname: Chiou
authors.forename: S
authors.initials: S
authors.lastname: Uffer
authors.forename: E
authors.initials: E
authors.lastname: Ballestrazzi
authors.forename: R E
authors.initials: RE
authors.lastname: Braunstein
authors.forename: R K
authors.initials: RK
authors.lastname: Forster
authors.forename: W W
authors.initials: WW
authors.lastname: Culbertson
authors.forename: H
authors.initials: H
authors.lastname: Boman
authors.forename: L
authors.initials: L
authors.lastname: Zografos
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003317:Corneal Dystrophies, Hereditary / Q000145:classification / Q000235:genetics*; D005091:Exons; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007438:Introns; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D005819:Genetic Markers